Our research deals principally with lipids of virulent tubercle bacilli. Cord factor and the mycobacterial sulfatides are two classes of trehalose-containing glycolipids from M. tuberculosis, which are implicated in virulence and in pathogenesis of the disease. Both substances also have antitumor activity in the line 10-strain-2 guinea pig system; but only cord factor (and closely related analogs) is active against certain murine fibrosarcomas. Our studies involve synthesis of pseudocord factors based upon "trehalose dicarboxylic acid" and on 6,6 -dideoxytrehalose - to fine inexpensive substitutes for natural cord factors, potentially useful in tumor immunotherapy; and to dissect the influence of defined structural changes on biological activities. The sulfatides, and other polyanionic agents, have been implicated in inducing phagosome-lysosome fusion dysfunction in cultured macrophages. Thus the mycobacterial sulfolipids are probably functional in promoting the intracellular survival of M. tuberculosis. Our current studies seek to define whether macrophage stimulation/activation abrogates the block to fusion; and the influence of this block on bactericidal activity.